RESUMO
AIM: In-hospital cardiac arrest occurs in >5000 children each year in the US and almost half will not survive to discharge. Animal data demonstrate that an immediate post-resuscitation burst of hypertension is associated with improved survival. We aimed to determine if systolic and diastolic invasive arterial blood pressures immediately (0-20â¯min) after return of spontaneous circulation (ROSC) are associated with survival and neurologic outcomes at hospital discharge. METHODS: This is a secondary analysis of the Pediatric Intensive Care Quality of CPR (PICqCPR) study of invasively measured blood pressures during intensive care unit CPR. Patients were eligible if they achieved ROSC and had at least one invasively measured blood pressure within the first 20â¯min following ROSC. Post-ROSC blood pressures were normalized for age, sex and height. "Immediate hypertension" was defined as at least one systolic or diastolic blood pressure >90th percentile. The primary outcome was survival to hospital discharge. RESULTS: Of 102 children, 70 (68.6%) had at least one episode of immediate post-CPR diastolic hypertension. After controlling for pre-existing hypotension, duration of CPR, calcium administration, and first documented rhythm, patients with immediate post-CPR diastolic hypertension were more likely to survive to hospital discharge (79.3% vs. 54.5%; adjusted ORâ¯=â¯2.93; 95%CI, 1.16-7.69). CONCLUSIONS: In this post hoc secondary analysis of the PICqCPR study, 68.6% of subjects had diastolic hypertension within 20â¯min of ROSC. Immediate post-ROSC hypertension was associated with increased odds of survival to discharge, even after adjusting for covariates of interest.
Assuntos
Parada Cardíaca/complicações , Parada Cardíaca/mortalidade , Hipertensão/etiologia , Diástole , Feminino , Humanos , Hipertensão/epidemiologia , Lactente , Masculino , Estudos Prospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
Studies of structure-activity relationships for the linker in a new series of metabotropic glutamate receptor 5 antagonists are presented together with in vitro and in vivo pharmacokinetic data.
Assuntos
Alcinos/química , Alcinos/farmacologia , Reagentes de Ligações Cruzadas/química , Piridinas/química , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Receptores de Glutamato Metabotrópico/metabolismo , Alcinos/síntese química , Alcinos/farmacocinética , Animais , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estrutura Molecular , Ratos , Receptor de Glutamato Metabotrópico 5 , Relação Estrutura-AtividadeRESUMO
Synthesis and some structure-activity relationships for a new series of propargyl ethers as mGluR5 antagonists are reported.
Assuntos
Alcinos/química , Alcinos/farmacologia , Piridinas/química , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Alcinos/síntese química , Concentração Inibidora 50 , Estrutura Molecular , Receptor de Glutamato Metabotrópico 5 , Receptores de Glutamato Metabotrópico/metabolismo , Relação Estrutura-AtividadeRESUMO
Structure-activity relationship investigations of the thiopyrimidine (1), an HTS hit with micromolar activity as a metabotropic glutamate receptor 5 (mGluR5) antagonist, led to compounds with sub-micromolar activity.
Assuntos
Pirimidinas/farmacologia , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Tionucleosídeos/farmacologia , Animais , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Humanos , Técnicas In Vitro , Fígado/efeitos dos fármacos , Microssomos/efeitos dos fármacos , Estrutura Molecular , Pirimidinas/síntese química , Pirimidinas/química , Ratos , Receptor de Glutamato Metabotrópico 5 , Estereoisomerismo , Relação Estrutura-Atividade , Tionucleosídeos/síntese química , Tionucleosídeos/químicaRESUMO
Fenobam (1) was developed by McNeil Laboratories as an anxiolytic agent with an unknown molecular target in the late 1970s. In a recent publication, it was revealed that fenobam is a non-competitive mGluR5 antagonist. Herein, we present the structure-activity relationship of fenobam and its analogues and similarities between the SAR of mGluR5 antagonism and the SAR of CNS properties originally reported by McNeil are discussed.